Synthesis and screening of 6‐alkoxy purine analogs as cell type‐selective apoptotic inducers in Jurkat cells

Abstract

Purines are ubiquitous structures in cell biology involved in a multitude of cellular processes, because of which substituted purines and analogs are considered excellent scaffolds in drug design. In this study, we explored the key structural features of a purine‐based proapoptotic hit, 8‐tert‐butyl‐9‐phenyl‐6‐benzyloxy‐9Hpurine (1), by setting up a library of 6‐alkoxy purines with the aim of elucidating the structural requirements that govern its biological activity and to study the cell selectivity of this chemotype. This was done by a phenotypic screening approach based on cell cycle analysis of a panel of six human cancer cell lines, including T cell leukemia Jurkat cells. From this study, two derivatives (12 and 13) were identified as Jurkat‐selective proapoptotic compounds, displaying superior potency and cell selectivity than hit 1.